Hepatomas have been shown to have a number of alterations in phospholipid composition. A key change is an increased level of lysophospholipids which are potent detergents. Further, the fatty acid composition of the phospholipid, in part determined by the monoacyl- diacyl cycle (Land's cycle), is different from normal liver. Both of these observations suggest changes in the metabolism of the lysophospholipids. It is the purpose of this project to identify the underlying alterations in lysophospholipid metabolism that leads to the unusual chemistry and structure of these lipids. Also, the synthesis and utilization of polyunsaturated fatty acids will be examined, since they too influence the physical-chemical nature of the membrane. The basic procedure will be to obtain Morris hepatoma in host rats, prepare and characterize subcellular fractions, study the phospholipases A and acyl CoA lysophospholipase acyl transferase activities, and compare these results with those obtained using normal rat liver. During this year's project we shall emphasize studies of these enzyme activities in mitochondria. The phospholipase A activity will be measured using endogenously labeled lipids primarily. The relationship of the Land's cycle to mitochondrial function will be examined. The functional studies will include the determination of the respiratory control ration, the ability of the mitochondrial membrane to maintain a pH gradient, and the morphologic integrity of the mitochondria as measured their swelling. We shall also continue our studies on the structural and physical chemical changes in hepatomas that relate to the Land's cycle. This will be done by monolayer and microelectrophoretic determination of the combined and individual lipids. Further, we shall relate these to the altered chemical composition of the membrane. These three approaches when used in combination should give a new insight into the altered energy utilization of cancerous tissue.